Inhibition of the Self-Assembly of Aβ and of Tau by Polyphenols: Mechanistic Studies
The amyloid-β (Aβ) peptide and tau protein are thought to play key neuropathogenic roles in Alzheimer’s disease (AD). Both Aβ and tau self-assemble to form the two major pathological hallmarks of AD: amyloid plaques and neurofibrillary tangles, respectively. In t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/12/2316 |
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| author | Qiuchen Zheng Micheal T. Kebede Merc M. Kemeh Saadman Islam Bethany Lee Stuart D. Bleck Liliana A. Wurfl Noel D. Lazo |
| author_facet | Qiuchen Zheng Micheal T. Kebede Merc M. Kemeh Saadman Islam Bethany Lee Stuart D. Bleck Liliana A. Wurfl Noel D. Lazo |
| author_sort | Qiuchen Zheng |
| collection | DOAJ |
| description | The amyloid-β (Aβ) peptide and tau protein are thought to play key neuropathogenic roles in Alzheimer’s disease (AD). Both Aβ and tau self-assemble to form the two major pathological hallmarks of AD: amyloid plaques and neurofibrillary tangles, respectively. In this review, we show that naturally occurring polyphenols abundant in fruits, vegetables, red wine, and tea possess the ability to target pathways associated with the formation of assemblies of Aβ and tau. Polyphenols modulate the enzymatic processing of the amyloid-β precursor protein and inhibit toxic Aβ oligomerization by enhancing the clearance of Aβ42 monomer, modulating monomer−monomer interactions and remodeling oligomers to non-toxic forms. Additionally, polyphenols modulate tau hyperphosphorylation and inhibit tau β-sheet formation. The anti-Aβ-self-assembly and anti-tau-self-assembly effects of polyphenols increase their potential as preventive or therapeutic agents against AD, a complex disease that involves many pathological mechanisms. |
| first_indexed | 2024-12-19T10:15:51Z |
| format | Article |
| id | doaj.art-3ddb5dfa912c4ce083e42c48eb0be1fe |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-19T10:15:51Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-3ddb5dfa912c4ce083e42c48eb0be1fe2022-12-21T20:26:12ZengMDPI AGMolecules1420-30492019-06-012412231610.3390/molecules24122316molecules24122316Inhibition of the Self-Assembly of Aβ and of Tau by Polyphenols: Mechanistic StudiesQiuchen Zheng0Micheal T. Kebede1Merc M. Kemeh2Saadman Islam3Bethany Lee4Stuart D. Bleck5Liliana A. Wurfl6Noel D. Lazo7Carlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USACarlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USACarlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USACarlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USACarlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USACarlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USACarlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USACarlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, MA 01610, USAThe amyloid-β (Aβ) peptide and tau protein are thought to play key neuropathogenic roles in Alzheimer’s disease (AD). Both Aβ and tau self-assemble to form the two major pathological hallmarks of AD: amyloid plaques and neurofibrillary tangles, respectively. In this review, we show that naturally occurring polyphenols abundant in fruits, vegetables, red wine, and tea possess the ability to target pathways associated with the formation of assemblies of Aβ and tau. Polyphenols modulate the enzymatic processing of the amyloid-β precursor protein and inhibit toxic Aβ oligomerization by enhancing the clearance of Aβ42 monomer, modulating monomer−monomer interactions and remodeling oligomers to non-toxic forms. Additionally, polyphenols modulate tau hyperphosphorylation and inhibit tau β-sheet formation. The anti-Aβ-self-assembly and anti-tau-self-assembly effects of polyphenols increase their potential as preventive or therapeutic agents against AD, a complex disease that involves many pathological mechanisms.https://www.mdpi.com/1420-3049/24/12/2316Alzheimer′s diseaseamyloid-β self-assemblytau self-assemblytau hyperphosphorylationamyloid assembliesneurofibrillary tanglespolyphenols |
| spellingShingle | Qiuchen Zheng Micheal T. Kebede Merc M. Kemeh Saadman Islam Bethany Lee Stuart D. Bleck Liliana A. Wurfl Noel D. Lazo Inhibition of the Self-Assembly of Aβ and of Tau by Polyphenols: Mechanistic Studies Molecules Alzheimer′s disease amyloid-β self-assembly tau self-assembly tau hyperphosphorylation amyloid assemblies neurofibrillary tangles polyphenols |
| title | Inhibition of the Self-Assembly of Aβ and of Tau by Polyphenols: Mechanistic Studies |
| title_full | Inhibition of the Self-Assembly of Aβ and of Tau by Polyphenols: Mechanistic Studies |
| title_fullStr | Inhibition of the Self-Assembly of Aβ and of Tau by Polyphenols: Mechanistic Studies |
| title_full_unstemmed | Inhibition of the Self-Assembly of Aβ and of Tau by Polyphenols: Mechanistic Studies |
| title_short | Inhibition of the Self-Assembly of Aβ and of Tau by Polyphenols: Mechanistic Studies |
| title_sort | inhibition of the self assembly of aβ and of tau by polyphenols mechanistic studies |
| topic | Alzheimer′s disease amyloid-β self-assembly tau self-assembly tau hyperphosphorylation amyloid assemblies neurofibrillary tangles polyphenols |
| url | https://www.mdpi.com/1420-3049/24/12/2316 |
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